Monoclonal antibodies are antibodies which have been produced by a cell line cloned from a single antibody producing cell. Monoclonal antibodies are extraordinarily pure, uniform and reproducible since each antibody is effective against a single antigenic determinant.
Monoclonal antibodies can be obtained in significant quantities from hybridoma cells. Hybridoma cells are fused cells resulting from the fusion of antibody producing cells with tumor cells. The initial work relating to the production of such hybridoma cells was done by Cesar Milstein and George Kohler employing mouse myeloma cells with spleen cells taken from mice immunized with sheep red blood cells. See, Kohler et al., Eur. J. Immunol., 6, 511-19 (1976); Kohler et al., Nature, 256, 495-7 (1975); and Milstein, Scientific American, 243 (4), 66-74 (1980).
More recently, Hilary Koprowski and colleagues have extended the original hybridoma work by developing hybridoma cell lines capable of producing monoclonal antibodies against specific viruses and tumors. See, U.S. Pat. Nos. 4,196,265 and 4,172,124, respectively. Wands and Zurawski further extended hybridoma technology to produce hybridoma cell lines capable of producing monoclonal antibodies to hepatitis virus. See U.S. Pat. No. 4,271,145. It has also been recently discovered that monoclonal IgM antibodies produced from hybridoma cell lines can be employed in certain immunoassays to improve the sensitivity and specificity thereof. See, U.S. application Ser. No. 188,735, filed Sep. 19, 1980, in the names of Jack R. Wands, Vincent R. Zurawski, and Hubert J. P. Schoemaker.
Even more recently, a monoclonal antibody, designated 1116 NS 19-9 (hereinafter "19-9 antibody"), was developed by Koprowski et al. by immunization of BALB/c mice with a human colorectal cancer cell line, SW1116. See Koprowski, H., Steplewski, Z., Mitchell, K., Herlyn, M., Herlyn, D., and Fuhrer, P., Colorectal carcinoma
antigens detected by hybridoma antibodies, Somatic Cell Genetics, 5, 957-972, (1979). It has been shown that the 19-9 antibody reacts with a carbohydrate antigenic determinant (hereinafter referred to as "CA 19-9") which has been identified as a sialylated lacto-N-fucopentaose II, an oligosaccharide which shares structural features with Lewis blood group substances. See Magnani, J., Nilsson, B., Brockhaus, M., Zopf, D., Steplewski, Z., Koprowski, H., Ginsburg, V., The antigen of a tumor--specific monoclonal antibody is a ganglioside containing sialylated lacto--N-Fucopentaose II, Fed. Proc. 41, 898, (1982).
In early studies using a competition radio-immunoassay, the 19-9 antibody was shown to have high sensitivity in identifying patients with gastrointestinal adenocarcinomas and to have high specificity for normal individuals. See Koprowski, H., Herlyn, H., Steplewski, Z., and Sears, H. F., Specific antigen in serum of patients with colon carcinoma, Science, 212, 53, (1981); and, Herlyn, M., Clark, W. H., Mastrangelo, J. J., Guerry, D., Elder, D. E., Larossa, D., Hamilton, R., Bondi, E., Tutkill, R., Steplewski, Z., Koprowski, H., Specific antigens to colorectal carcinoma in sera of patients are detected by monoclonal antibodies, Cancer Res. 40, 3602-3609, (1982). The CA 19-9 epitope has also been identified on a glycolipid extracted from SW1116 cells and from meconium, as well as on a glycoprotein from SW1116 cells. See Magnani, J., Brockhaus, M., Smith, D., Ginsburg, V., Blaszcyk, M., Mitchell, D., Steplewski, Z., and Koprowski, H., A Monoclonal Antibody Defined Antigen of colon Carcinoma, Science 212, 55, (1981).